Some of the psychosis-only-associated SNPs found in the d-amino acid oxidase activator (DAOA) and the kynurenine 3-monooxygenase (KMO) genes have previously been reported to be associated with schizophrenia.
In a prospective cohort (follow-up=2.4-14.9 years) of 225 individuals at ultra-high risk (UHR) for psychosis, we assessed haplotype-tagging single-nucleotide polymorphisms (htSNPs) spanning NRG1 and DAOA for their association with transition to psychosis, using Cox regression analysis.
The D-Amino acid oxidase activator (G72 or DAOA) is believed to play a key role in the regulation of central glutamatergic transmission which is seen to be altered in psychosis.
Assessment of nine common variants in the DAOA/G72 locus yielded two variants with the predictive value for symptom progression: all four probands with the rs1341402 CC genotype developed psychosis compared with 17 out of 78 probands with the TT or CT genotypes (chi(2) = 12.348; df = 2; p = 0.002).
The DAOA gene may play a role in predisposing individuals to a mixed phenotype of psychosis and mania and to impairments in related neuropsychological traits.
Despite being originally described as a schizophrenia susceptibility locus, our data suggest that variation at the DAOA/G30 locus does not primarily increase susceptibility for prototypical schizophrenia or psychosis.
In a logistic regression, "persecutory delusions" were found to be the only significant explanatory variable for the DAOA/G30 risk genotype among 21 OPCRIT symptoms of psychosis.